Erythema Multiforme (Notes & Video)
Erythema multiforme (EM) is a blistering and ulcerative, inflammatory condition affecting the skin and mucous membranes.
The term “multiforme” in erythema multiforme indicates the many variations of skin lesions that the disease can manifest with --> macules, papules, blisters and plaques.
EM depending on the severity and extent of involvement of mucous membranes --> classified as EM minor and EM major.
EM minor usually involves the skin, without or with the involvement of at least one mucosal site (usually the oral cavity) and EM major could involve two or more mucosal sites apart from the skin.
💡Know Thy Facts!
Steven-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) were thought to be severe variants of EM. However they are now, not considered to be a part of the EM spectrum and are designated as distinct entities.ETIOLOGY
EM is known to be triggered by microbes and less commonly, drugs.
Herpes simplex virus is most commonly implicated in causing the disease. Other organisms implicated --> Mycoplasma pnuemoniae and Histoplasma capsulatum.
A variety of drugs (rarely trigger EM) like sulphanomides, cephalosporins, barbiturates, NSAIDs and corticosteroids are known to trigger EM.
💡Know Thy Facts!
In general, viral infections (mostly herpes simplex) tend to trigger EM minor & major, while drugs induce SJS & TEN. This is however not mandatory, as there are rare cases of drug induced EM and viral infections triggering SJS and TEN.PATHOGENESIS
EM is hypothesized to be a cell mediated immune response.
CD4 T cells recognize viral antigens and release a cytokine called IFNγ, which is known to upregulate more cytokines.
This results in a cascade of inflammatory reactions resulting in epithelial damage.
Similarly a pro-inflammatory cytokine called TNFα has been implicated in tissue damage in case of drug induced disease.
CLINICAL FEATURES
EM affects young adults between 20-40 years, usually men.
It may have a sudden onset but usually has prodromal symptoms like fever, malaise and vomiting a week prior to the onset of the disease.
EM MINOR
EM minor involves the skin, without or with the involvement of at least one mucosal site usually the oral cavity.
Skin lesions usually appear at the extremities --> arms & legs, head & neck.
Skin lesions are symmetrical and start appearing as macules or erythematous papules --> progress to become characteristic “target lesions” also called “bull’s eye lesions”.
💡WHAT ARE TARGET LESIONS?
Target lesions are concentric ring like lesions with varying shades of erythema. These are usually flat or may be raised at times, have an erythematous disc at the centre with paler rings surrounding it. They are usually less than 3 cms in size. Oral lesions begin as red/erythematous macules --> progress to become blisters --> soon rupture leaving behind raw, painful erosions and ulcers.
Lesions usually appear in non-keratinized sites like the buccal mucosa, lips, tongue, floor of the mouth and soft palate. Gingiva is usually not involved.
Patients commonly present with swollen, ulcerated and crusted lips.
EM MAJOR
EM major is a more severe form of the disease and could involve two or more mucosal sites apart from the skin.
Otherwise the oral and skin manifestations are the same as EM minor.
Other mucous membranes that may be affected --> ocular, laryngeal, oesophageal, genital.
HISTOPATHOLOGY FEATURES
Histopathologic features are not diagnostic of EM.
Spinous layer is edematous --> shows epithelial necrosis in the supra-basal and basal layers --> results in a supra-basilar/intra-epithelial and sub-epithelial blister formation respectively.
Connective tissue may show inflammation below epithelium consisting of lymphocytes and macrophages/monocytes.
TREATMENT
EM is a self-limiting disease --> resolves in a few weeks (2-6 weeks).
Acyclovir therapy is initiated if disease is suspected to have a viral etiology.
Symptomatic and supportive treatment --> oral irrigation, topical anesthetics to reduce pain and fluid intake.
✅HIGHLIGHTS - VIVA & ENTRANCE EXAM PERSPECTIVE
The term “multiforme” in erythema multiforme indicates the many variations of skin lesions that the disease can manifest with macules, papules, blisters and plaques.
EM minor usually involves the skin, without or with the involvement of at least one mucosal site (usually the oral cavity) and EM major could involve two or more mucosal sites apart from the skin.
Herpes simplex virus is most commonly implicated in causing the disease.
Characteristic feature of EM is the appearance of “target lesions”/ “bull’s eye lesions” on the skin.
Patients commonly present with swollen, ulcerated and crusted lips.
EM may show a supra-basilar/intra-epithelial as well as a sub-epithelial blister formation.
📖REFERENCES AND FURTHER READING
Farthing P, Bagan JV, Scully C. Mucosal disease series. Number IV. Erythema multiforme. Oral Dis. 2005;11(5):261-7.
Baillis B, Maize JC. Treatment of recurrent erythema multiforme with adalimumab as monotherapy. JAAD Case Reports. 2017;3(2):95-97.
Oliveira, L.R, Zucoloto S, Erythema Multiforme Minor: A Revision. Am. J. Infect. Dis. 2008; 4(4):224-31.
Neville BW, Damm DD, Allen CM, Chi A. Oral and Maxillofacial Pathology. South Asian ed. Elsevier; 2016.
Rajendran R, Sivapathasundaram B. Shafer’s Textbook of Oral Pathology. 7th ed. Elsevier; 2012.
Regezzi JA, Sciubba JJ, Jordan RCK. Oral Pathology: Clinical Pathologic Correlations. 5 th ed. Elsevier; 2007.
Sapp JP, Eversole LR, Wysocki GP. Contemporary Oral and Maxillofacial Pathology. 2 nd ed. Mosby; 2004.